Project Summary/Abstract Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Metastasized colorectal cancer (mCRC), primarily in liver, is the predominate factor for the mortality of CRC patients. Treatment of CRC liver metastases is essential to the survival of mCRC patients. Currently, anti-angiogenesis therapy plays a significant role in the treatment of CRC liver metastases. Early and accurate prediction of response to anti-angiogenesis therapy is of vital clinical significance because: 1) early identification of nonresponders can expedite the adjustment of treatment regimens to avoid disease progression and spare patients from unnecessary toxicity and medical expense of ineffective therapies; 2) reliable response assessment can help individualize treatment strategy and optimize dose and time course of therapy to achieve maximal treatment efficacy; 3) an early and accurate predictive biomarker is also very beneficial to development of new therapy agents by providing a reliable surrogate endpoint for clinical trials. At present, however, a reliable treatment response assessment tool for anti-angiogenesis therapy does not exist clinically. To fill this gap, here we propose to develop a novel ultrasound microvessel imaging technology, VesselQuest, to early predict anti-angiogenesis therapy response by examining tumor micro-vasculature with quantitative hemodynamic and morphologic measurements. VesselQuest can accurately measure a wide dynamic range of microvessel flow speed and offers a spatial super-resolution that cannot be achieved by current clinical imaging modalities. Similar to other ultrasound techniques, VesselQuest is also noninvasive, safe, and cost effective. These features of VesselQuest provide excellent potential for clinical assessment of colorectal liver metastases treatment response to anti-angiogenic therapy. Aims 1 and 2 of this study will be focused on technical development of VesselQuest, paving the way for the aims 3 and 4 of the study which will be focused on validating VesselQuest on an animal tumor model and conducting a pilot clinical study on CRC liver metastases patients to assess treatment response to anti-angiogenesis therapy. Successful completion of this project will provide a novel and viable technology for early prediction of anti-angiogenic therapy to improve treatment outcome and survival of CRC liver metastases patients. Technologies developed for this project can also be used for assessment of emerging novel treatment method such as immunotherapy.